A Preclinical Model for Studying Herpes Simplex Virus Infection.

Area of Science:

• Virology
• Dermatology
• Pharmacology

Background:

• Herpes simplex virus (HSV) infections cause significant illness, with acyclovir resistance posing a clinical challenge, particularly in immunocompromised individuals.
• Development of novel antiviral compounds is crucial to overcome drug resistance and improve therapeutic outcomes for HSV infections.

Purpose of the Study:

• To establish and validate an ex vivo human skin model for testing antiviral drugs against HSV-1.
• To evaluate the efficacy of pritelivir, a helicase-primase inhibitor, compared to acyclovir in an HSV-1 ex vivo skin infection model.

Main Methods:

• An ex vivo human abdominal skin model was established using microneedle pretreatment to mimic HSV-1 infection.
• Histological analysis identified HSV-1-specific cytopathic effects and immune responses, including changes in nectin-1, NF-κB, IRF3, and MxA.
• The efficacy of pritelivir and acyclovir in inhibiting HSV-1 replication was assessed using this model.

Main Results:

• The ex vivo skin model successfully replicated HSV-1 infection, showing characteristic histological changes and molecular signaling.
• Pritelivir demonstrated comparable efficacy to acyclovir in inhibiting HSV-1 replication within the established skin model.
• The study identified key molecular markers of HSV-1 infection in the skin model, aiding in drug efficacy assessment.

Conclusions:

• The developed ex vivo human skin model serves as a valuable preclinical platform for evaluating antiviral drugs against HSV.
• Pritelivir is a promising therapeutic candidate, showing comparable efficacy to acyclovir and potential as an alternative for acyclovir-resistant HSV strains.
• This model bridges the gap between in vitro and in vivo studies, advancing preclinical drug screening for HSV infections.